1. Field of the Invention
The present invention relates to 1-acetylaminotricycloundecane and processes for the preparation thereof.
More particularly, the present invention relates to 1-acetylaminotricyclo [4.3.1.1.sup.2,5 ] undecane of formula (I) and processes for the preparation of this compound by reacting a tricyclo [4.3.1.1.sup.2,5 ] undecane derivative of formula (II) or endo-2-hydroxymethyl-exo-2,3-trimethylenenorbornane of formula (III) with acetonitrile in the presence of sulfuric acid: ##STR1##
1-Acetylaminotricyclo [4.3.1.1.sup.2,5 ] undecane of formula (I) which is the desired product of the present invention is very useful as an intermediate. If this compound is hydrolyzed and then the corresponding amino derivative thus obtained is neutralized with hydrochloric acid, 1-aminotricyclo [4.3.1.1.sup.2,5 ] undecane hydrochloride is obtained which has a strong antiviral activity and which is very useful as an ingredient of medicines for human beings and animals.
Elementary analysis and mass spectrum analysis of 1-acetylaminotricyclo [4.3.1.1.sup.2,5 ] undecane synthesized according to the present invention proves that this is a compound containing only one nitrogen atom. The structure of the compound has been confirmed from the fact that the absorptions peculiar to amide (3325, 1650, 1550 cm.sup.-1) appear in the infrared absorption spectrum.
In the preparation of the compound of formula (I) of the present invention, a tricyclo [4.3.1.1.sup.2,5 ] undecane derivative of formula (II) or endo-2-hydroxymethyl-exo-2,3-trimethylenenorbornane of formula (III) is used as the starting compound and it is reacted with acetonitrile in the presence of sulfuric acid.
Acetonitrile is used in an amount of 1 to 100 moles, preferably 10 to 50 moles, per one mole of the starting compound. Sulfuric acid is used in an amount of 1 to 20 moles, preferably 5 to 10 moles, per one mole of the starting compound. The concentration of the sulfuric acid is in the range of 80 to 100%, preferably 90 to 100%. The reaction temperature is in the range of from -20.degree. C to 82.degree. C, preferably 20.degree. to 50.degree. C. Under the above reaction conditions, the reaction is completed in 24 hours. Although there can be used any inert solvent which does not adversely affect the reaction, it is preferred to carry out the reaction without a solvent in view of the ease of after-treatment.
If the tricyclo [4.3.1.1.sup.2,5 ] undecane derivative of formula (II) is used as the starting compound, the reaction which takes place is the so-called Ritter reaction.
If endo-2-hydroxymethyl-exo-2,3-trimethylenenorbornane of formula (III) is used as the starting compound, isomerization of the skeleton and the Ritter reaction take place simultaneously. A process of converting endo-2-hydroxymethyl-exo-2,3-trimethylenenorbornane (III) into a compound possessing the tricyclo [4.3.1.1.sup.2,5 ] undecane skeleton by acid catalytic isomerization reaction has been proposed by two of the inventors and another author Lukaishi et al, "J. Chem. Soc." Perkin Trans., 1, 789 (1975)). The present invention has been accomplished on the basis of the discovery that if said reaction is carried out in the presence of acetonitrile, the Ritter reaction also immediately takes place to form 1-acetylaminotricyclo [4.3.1.1.sup.2,5 ] undecane, according to the following reaction scheme: ##STR2##
1-Bromotricyclo [4.3.1.1.sup.2,5 ] undecane used as a starting compound of formula (II) in the present invention can be synthesized by, for example, brominating tricyclo [4.3.1.1.sup.2,5 ] undecane with liquid bromine or by brominating tricyclo [4.3.1.1.sup.2,5 ] undecane-1-ol with thionyl bromide. 1-Chlorotricyclo [4.3.1.1.sup.2,5 ] undecane can by synthesized by chlorinating tricyclo [4.3.1.1.sup.2,5 ] undecane-1-ol with thionyl chloride. Tricyclo [4.3.1.1.sup.2,5 ] undecane-1-ol can be synthesized by hydrolyzing 1-chloro- or 1-bromotricyclo [4.3.1.1.sup.2,5 ] undecane or by isomerizing endo-2-hydroxymethyl-exo-2,3-trimethylenenorbornane in aqueous sulfuric acid solution.
Endo-2-hydroxymethyl-exo-2,3-trimethylenenorbornane used as the starting compound of formula (III) can be obtained easily by, for example, reacting exo-2,3-trimethylene-5-norbornene or exo-6-hydroxy-exo-2,3-trimethylenenorbornane with formic acid or carbon monoxide in sulfuric acid to effect esterification, thereby forming endo-2-carboxy-exo-2,3-trimethylenenorbornane (H. Koch & W. HAAF, "Ann." 638, 111 (1960)) and then reducing the ester (Lakanishi et al "J. Chem. Soc.", Perkin Trans., 1, 789 (1975)).